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Spinazzi 2019 Proc Natl Acad Sci U S A
Additional label 2019-02  + , Amplex UltraRed  + , Calcium Green 5N  + , Safranin  +
Coupling states ET  + , LEAK  + , OXPHOS  +
Diseases Neurodegenerative  +
Enzyme Complex I  + , Complex II;succinate dehydrogenase  + , Complex III  + , Complex IV;cytochrome c oxidase  + , Complex V;ATP synthase  +
Has abstract The mitochondrial intramembrane rhomboid p
The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions ''in vitro'', but its physiological role ''in vivo'' remains unclear. Here we show that ''Parl'' ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional PARL deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline ''Parl'' KOs, demonstrating the vital role of PARL in neurological homeostasis. Genetic modification of two major PARL substrates, PINK1 and PGAM5, do not modify this severe neurological phenotype. ''Parl''<sup>-/-</sup> brain mitochondria are affected by progressive ultrastructural changes and by defects in Complex III (CIII) activity, coenzyme Q (CoQ) biosynthesis, and mitochondrial calcium metabolism. PARL is necessary for the stable expression of TTC19, which is required for CIII activity, and of COQ4, which is essential in CoQ biosynthesis. Thus, PARL plays a previously overlooked constitutive role in the maintenance of the respiratory chain in the nervous system, and its deficiency causes progressive mitochondrial dysfunction and structural abnormalities leading to neuronal necrosis and Leigh-like syndrome.
neuronal necrosis and Leigh-like syndrome.  +
Has editor [[Plangger M]]  +
Has info [ PMID: 30578322] »[[File:O2k-brief.png|36px|link=|O2k-brief]]  +
Has publicationkeywords Leigh syndrome  + , Mitochondria  + , Neurodegeneration  + , Respiratory chain  + , Rhomboid protease  +
Has title Spinazzi M, Radaelli E, Horré K, Arranz AM
Spinazzi M, Radaelli E, Horré K, Arranz AM, Gounko NV, Agostinis P, Maia TM, Impens F, Morais VA, Lopez-Lluch G, Serneels L, Navas P, De Strooper B (2019) PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome. Proc Natl Acad Sci U S A 116:277-86.
rome. Proc Natl Acad Sci U S A 116:277-86.  +
Instrument and method O2k-Fluorometer  + , Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Genetic knockout;overexpression  + , Respiration  + , mtDNA;mt-genetics  +
Pathways CIV  + , N  + , NS  + , ROX  + , S  +
Preparation Intact cells  + , Isolated mitochondria  + , Permeabilized cells  +
Respiration and regulation Calcium  + , mt-Membrane potential  +
Tissue and cell Nervous system  +
Was published by MiPNetLab BE Leuven Spinazzi M +
Was published in journal Proc Natl Acad Sci U S A +
Was published in year 2019  +
Was written by Spinazzi M + , Radaelli E + , Horre K + , Arranz AM + , Gounko NV + , Agostinis P + , Maia TM + , Impens F + , Morais VA + , Lopez-Lluch G + , Serneels L + , Navas P + , De Strooper B +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
09:40:57, 26 July 2019  +
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